Learning Why Type 2 Quickly Hurts Kids’ Kidneys

Jane Kim, MD

OccupationPediatric Endocrinologist, University of California–San Diego School of Medicine

FocusPediatrics

ADA Research FundingInnovation

In 1979, the American Diabetes Association stopped using the term “adult-onset diabetes.” In 1997, the disease was officially renamed type 2 diabetes by an international panel. The change was, in part, a reflection of a growing realization that the old term was no longer accurate.

In the decades since, the epidemic of childhood obesity and type 2 diabetes has only grown. Between 2001 and 2009, one study found, pediatric type 2 cases climbed 30 percent. “We’ve seen a big rise in the rates of pediatric obesity. Children are coming in with diabetes in their teens,” says Jane Kim, MD, a pediatric endocrinologist at the University of California–San Diego School of Medicine. “Their parents might have been diagnosed at 30 or 40, and their grandparents in their 50s or 60s.”

As the number of children diagnosed with type 2 climbs, researchers are realizing that not all people with type 2 are equally affected by complications such as kidney disease, eye disease, and nerve damage.

Here, too, the news is not good. Pediatric diabetes not only occurs early in life but may also be more severe. “Type 2 in children seems to be more aggressive than in adults,” Kim says. “In adults, there can be a long period between diagnosis and when complications occur. Kids’ complications can occur within a few years of diagnosis.”

Researchers have also found that children who develop type 2 often respond poorly, or not at all, to the common diabetes drug metformin. That robs many young patients of a relatively safe pill option and requires many to begin insulin injections.

While scientists are familiar with the phenomenon, the biology behind it remains a mystery. “We don’t understand everything about it, but my feeling is it’s intrinsically different,” Kim says. “Maybe the rate of beta cell failure is more aggressive—they require more insulin, sooner, and that can’t be reversed.”

With the help of a grant from the American Diabetes Association, Kim is looking for ways to determine, long before the damage is done, which kids are most at risk for developing complications. Kidney disease, a complication she sees often in kids with type 2 diabetes and one that can be particularly damaging and difficult to treat, is her specific focus.

To figure out who is at highest risk for kidney problems, Kim has set up a study looking at 90 kids without kidney disease between 13 and 19. Thirty of them have type 2 diabetes, 30 are obese but don’t have diabetes, and 30 are normal-weight teens without diabetes.

Kim is testing urine samples to see if there’s something in the body chemistry of the kids with diabetes that sets them apart from their peers. To do that, she looks at metabolites, chemical compounds produced by the body as it generates energy and processes waste. “It’s like a chemical fingerprint of what’s happening in the body,” she says.

In each urine sample, Kim detects between 100 and 300 different metabolites. By measuring the types and amounts of each, she can learn more about what’s going on inside the body. Proteins called branched chain amino acids, for example, are more concentrated in people who develop type 2 diabetes; Kim’s study can measure the metabolites involved in building up and breaking down these proteins to understand why some people have more of them.

Kim expects to see differences in the metabolites of the three groups of kids and perhaps even differences within each group. “With this first snapshot, we’re trying to understand how kids with diabetes are different and how diabetes has affected their metabolism—and what’s happening with their kidneys,” she says.

After gathering and analyzing this first data set, she will apply for funding to follow the kids with diabetes over time to see if they later develop complications. “The idea would be to see, over time, if the metabolic profiles are actually predictive,” she says. “Then we could create a diagnostic signature we could use to predict chronic kidney disease complications.”

With a more reliable way to diagnose early those most at risk for complications, doctors could tailor treatment for those most in need. “The goal is to stave complications off, or at least treat them more effectively,” Kim says.

Help Support Diabetes Science

Join the Summit Circle, the ADA’s society of individuals who make a planned gift. Please call 1-888-700-7029 or find out more at diabetes.org/giving.